Pre-invasive cervical disease and cervical carcinoma

Until a few years ago cervical cancer was one of the commonest type of cancer in women worldwide. Its incidence decreased dramatically following the implementation of the Papanicolaou (Pap) smear as a screening procedure. The Pap smear can detect a wide range of abnormalities of the cervix from benign cellular changes to precancerous conditions. Part of this review, will focus on this issue, specifically the abnormal and/or possibly precancerous findings that can be found in a Pap smear result. These will be classified according to the Bethesda system. One must emphasize here that most of these abnormalities regress on their own and do not need specific treatment. Yet, findings like the High-grade Squamous Intraepithelial Lesion (HSIL) have a high rate of progression to cancer and necessitate immediate management. The other half of this review will focus on cervical cancer in itself, a malignant and therefore invasive disease which, like all other cancers, can be fatal if left untreated. The extent of spread of the cancer is determined by the staging system, here described according to the International Federation of Gynecology and Obstetrics (FIGO). Staging is an important means of evaluating the treatment plans used.peer-reviewe

The human papillomaviruses (HPVs) and HPV DNA testing

The fact that some viruses act as carcinogens has long since been known. Amongst these viruses are some genotypes of the Human Papillomaviruses (HPVs). HPV is most frequently associated with cervical cancer, that is, cancer of the cervix or neck of the uterus. In fact, 95-100% of all cervical cancers are caused by infection with HPV. HPV also causes a high proportion of other anogenital cancers. In 1995, the International Agency for Research on Cancer (IARC) concluded that HPV types 16 and 18 are carcinogenic to humans; HPV types 31 and 33 are probably carcinogenic to humans whilst some HPV types other than 16, 18, 31 and 33 are possibly carcinogenic to humans. This review focuses first on the structure, classification and genome of these particular viruses. Particular attention is given to those features that play a role in the carcinogenicity of particular HPV genotypes. Given the close association between HPV and cervical cancer, detecting the presence of HPV in a particular patient and more specifically, the presence of particular genotypes of HPV, may give an indication of the likelihood of progression to precancerous and cancerous changes in the cervix. In fact, there is much evidence that screening of women with both cytology and HPV DNA tests increases sensitivity for detection of Cervical Intraepithelial Neoplasia (CIN) 3 or cancer sufficiently to permit longer screening intervals than with cytology alone. However, it is important to realize that the presence of HPV does not mean that a woman has or will develop cervical disease. Thus, there is still a dilemma as regards the real utility of HPV DNA testing. Screening and diagnostic procedures for cervical cancer will be discussed in the second part of this review, with special emphasis on HPV DNA testing. The benefits of HPV DNA testing in specific situations will be highlighted, particularly in the case of a diagnosis of Atypical Squamous Cell of Undetermined Significance (ASCUS).peer-reviewe

The mechanisms of HPV-induced carcinogenesis and the HPV vaccine

Human Papillomavirus (HPV) is the most common sexually transmitted virus. It is estimated that 75% of sexually active adults transmit HPV at some instance during their life. It has long since been known that infection with particular genotypes of this virus is a necessary factor for the development of cervical cancer. In fact, the DNA of this virus is found in 100% of histologically-confirmed cervical cancers. Cervical cancer is a frequent cause of female morbidity and mortality, especially in developing counties. The first part of this study will focus on the way in which infection with specific genotypes of this virus can lead to the development of neoplasia. This will be done in part by explanation of the life cycle of this virus as well as by clarification of the function of the 2 oncogenes E6 and E7 that this virus possesses as part of its genome. It must be kept in mind that not all genotypes of this virus are carcinogenic. In fact, the genotypes that are most strongly associated with cervical cancer are HPV-16 and HPV-18, 2 genotypes that were described by the International Association of Research on Cancer (IARC) as definite human carcinogens. These two genotypes also fall under the heading of high-risk viruses, also because of their oncogenic potential. Given the fact that infection with HPV is an essential step in the development of cervical cancer, prevention of infection by vaccination can reduce the incidence of this cancer. In June 2006, the Food and Drug Administration (FDA) approved an HPV vaccine, Gardasil, for clinical use in females aged 9-26. This vaccine protects against 4 genotypes of HPV, two of which are the above-mentioned HPV-16 and HPV-18. These 2 genotypes together are responsible for over 70% of cervical cancers. It is thus, hoped that this vaccine will have major benefit on a global scale. The 2nd part of this review will focus on diverse issues related to the HPV vaccine. A brief review of the experiments.peer-reviewe

Physics opportunities with future proton accelerators at CERN

We analyze the physics opportunities that would be made possible by upgrades of CERN's proton accelerator complex. These include the new physics possible with luminosity or energy upgrades of the LHC, options for a possible future neutrino complex at CERN, and opportunities in other physics including rare kaon decays, other fixed-target experiments, nuclear physics and antiproton physics, among other possibilities. We stress the importance of inputs from initial LHC running and planned neutrino experiments, and summarize the principal detector R&D issues.Comment: 39 page, word document, full resolution version available from http://cern.ch/pofpa/POFPA-arXive.pd

Relationship of hyperglycaemia, hypoglycaemia, and glucose variability to atherosclerotic disease in type 2 diabetes

Objective: Type 2 diabetes mellitus (T2DM) is known to be associated with increased cardiovascular risk. The aim of this study was therefore to investigate the independent effects of hyperglycaemia, hypoglycaemia, and glucose variability on microvascular and macrovascular disease in T2DM. Methods. Subjects with T2DM of 7.8mmol/L (β=15.83, p=0005) was the sole independent predictor of albuminuria in generalised linear regression. Conclusions. This study demonstrates that hypoglycaemia is associated with the occurrence of atherosclerotic disease while hyperglycaemia is associated with microvascular disease in a Caucasian population with T2DM of recent duration.peer-reviewe

Using switching multiple models for the automatic detection of spindles

Sleep EEG data is characterised by various events that allow for the identification of the different sleep stages. Stage 2 in particular is characterised by two morphologically distinct waveforms, specifically spindles and K-complexes. Manual scoring of these events is time consuming and risks being subjectively interpreted; hence there is the need of robust automatic detection techniques. Various approaches have been adopted in the literature, ranging from period-amplitude analysis, to spectral analysis and autoregressive modelling. Most of the adopted techniques follow an episodic approach where the goal is to identify whether an epoch of EEG data contains an event, such as a spindle, or otherwise. The disadvantage of this approach is that it requires the data to be segmented into epochs, risking that an event falls at an epoch boundary, and it has low temporal resolution. This work proposes the use of an autoregressive switching multiple model for the automatic segmentation and labelling of Stage 2 sleep EEG data characterised by spindles and K-complexes. When this modelling technique was used to identify spindles from background EEG, quantitative results based on a sample by sample basis gave a sensitivity score between 72.39% to 87.51%, depending to which scorer performance was compared. This score corresponds to a specificity that ranges between 78.89% and 90.55% and which increases to a range between 75.52% and 94.64% when performance is measured on an event basis instead [1]. This performance compares well with other spindle detection techniques published in the literature [2,3]. The advantage of the proposed technique is that it allows for the continuous segmentation of EEG data, it offers a unified framework to detect multiple events with little training data, and it can also be extended to a semi-supervised approach. The latter, which has also been applied to Stage 2 sleep EEG data, can identify new states in real time, providing a solution that not only replaces the time consuming manual scoring process but it may also provide the clinician with new insights on the data that is being analysed.peer-reviewe

Dual adaptive dynamic control of mobile robots using neural networks

This paper proposes two novel dual adaptive neural control schemes for the dynamic control of nonholonomic mobile robots. The two schemes are developed in discrete time, and the robot's nonlinear dynamic functions are assumed to be unknown. Gaussian radial basis function and sigmoidal multilayer perceptron neural networks are used for function approximation. In each scheme, the unknown network parameters are estimated stochastically in real time, and no preliminary offline neural network training is used. In contrast to other adaptive techniques hitherto proposed in the literature on mobile robots, the dual control laws presented in this paper do not rely on the heuristic certainty equivalence property but account for the uncertainty in the estimates. This results in a major improvement in tracking performance, despite the plant uncertainty and unmodeled dynamics. Monte Carlo simulation and statistical hypothesis testing are used to illustrate the effectiveness of the two proposed stochastic controllers as applied to the trajectory-tracking problem of a differentially driven wheeled mobile robot.peer-reviewe

The nonlinear electromigration of analytes into confined spaces

We consider the problem of electromigration of a sample ion (analyte) within a uniform background electrolyte when the confining channel undergoes a sudden contraction. One example of such a situation arises in microfluidics in the electrokinetic injection of the analyte into a micro-capillary from a reservoir of much larger size. Here the sample concentration propagates as a wave driven by the electric field. The dynamics is governed by the Nerst-Planck-Poisson system of equations for ionic transport.A reduced one dimensional nonlinear equation describing the evolution of the sample concentration is derived.We integrate this equation numerically to obtain the evolution of the wave shape and determine how the the injected mass depends on the sample concentration in the reservoir.It is shown that due to the nonlinear coupling of the ionic concentrations and the electric field, the concentration of the injected sample could be substantially less than the concentration of the sample in the reservoir.Comment: 14 pages, 5 Figures, 1 Appendi

Parametric Modelling of EEG Data for the Identification of Mental Tasks

Electroencephalographic (EEG) data is widely used as a biosignal for the identification of different mental states in the human brain. EEG signals can be captured by relatively inexpensive equipment and acquisition procedures are non-invasive and not overly complicated. On the negative side, EEG signals are characterized by low signal-to-noise ratio and non-stationary characteristics, which makes the processing of such signals for the extraction of useful information a challenging task.peer-reviewe

Crystalline phases involved in the hydration of calcium silicate-based cements: Semi-quantitative Rietveld X-ray diffraction analysis

Chemical comparisons of powder and hydrated forms of calcium silicate cements (CSCs) and calculation of alterations in tricalcium silicate (Ca3SiO5) calcium hydroxide (Ca(OH)2) are essential for understanding their hydration processes. This study aimed to evaluate and compare these changes in ProRoot MTA, Biodentine and CEM cement. Powder and hydrated forms of tooth coloured ProRoot MTA, Biodentine and CEM cement were subjected to X-ray diffraction (XRD) analysis with Rietveld refinement to semi-quantitatively identify and quantify the main phases involved in their hydration process. Data were reported descriptively. Reduction in Ca3SiO5 and formation of Ca(OH)2 were seen after the hydration of ProRoot MTA and Biodentine; however, in the case of CEM cement, no reduction of Ca3SiO5 and no formation of Ca(OH)2 were detected. The highest percentages of amorphous phases were seen in Biodentine samples. Ettringite was detected in the hydrated forms of ProRoot MTA and CEM cement but not in Biodentine